In our previous study, we have shown the rapid, transient induction of the proto-oncogene c-fos mRNA in the cardiac tissues of the mouse, rat, and hamster following the administration of alpha- or beta-adrenergic agonists, prostaglandin E1, or histamine. We propose to extend these studies to investigate the expression of c-fos, c-myc, and c-jun genes during the life-span of the rat, and the induction of these genes by adrenergic genes during the life-span of the rat, and the induction of these genes by adrenergic agonists and histamine. We will establish, by using immunocytochemical techniques, the cellular localization of Fos, Myc, and Jun proteins in the heart, and will correlate the expressions of these three genes with cardiac necrosis produced by isoproterenol. The underlying major hypothesis of this proposal is that in the heart the expression of c-fos, c-myc, and c-jun genes is one of the earliest response to stress mediated in part by receptors for catecholamines, histamine, prostaglandin(s), and perhaps other agonists. These proto-oncogenes, encoding regulatory nuclear proteins, lie at the distal end of signaling cascades, and affect or modulate long-term changes in gene expression in response to cell surface stimulation (e.g. by growth factors and peptide hormones) and stress. The significance, and novelty, of the proposed research are that it deals with a hitherto unknown manifestation of cardiac response to adrenergic stimulation and stress that may play a role in cardiac degeneration, necrosis, and hypertrophy. Since cardio-vascular disease remain the leading cause of death in the United States, the relevance of the proposed research to health care is obvious.